1.
Broadening horizons: the role of ferroptosis in cancer.
Chen, X, Kang, R, Kroemer, G, Tang, D
Nature reviews. Clinical oncology. 2021;(5):280-296
Abstract
The discovery of regulated cell death processes has enabled advances in cancer treatment. In the past decade, ferroptosis, an iron-dependent form of regulated cell death driven by excessive lipid peroxidation, has been implicated in the development and therapeutic responses of various types of tumours. Experimental reagents (such as erastin and RSL3), approved drugs (for example, sorafenib, sulfasalazine, statins and artemisinin), ionizing radiation and cytokines (such as IFNγ and TGFβ1) can induce ferroptosis and suppress tumour growth. However, ferroptotic damage can trigger inflammation-associated immunosuppression in the tumour microenvironment, thus favouring tumour growth. The extent to which ferroptosis affects tumour biology is unclear, although several studies have found important correlations between mutations in cancer-relevant genes (for example, RAS and TP53), in genes encoding proteins involved in stress response pathways (such as NFE2L2 signalling, autophagy and hypoxia) and the epithelial-to-mesenchymal transition, and responses to treatments that activate ferroptosis. Herein, we present the key molecular mechanisms of ferroptosis, describe the crosstalk between ferroptosis and tumour-associated signalling pathways, and discuss the potential applications of ferroptosis in the context of systemic therapy, radiotherapy and immunotherapy.
2.
Manipulating Intratumoral Fenton Chemistry for Enhanced Chemodynamic and Chemodynamic-Synergized Multimodal Therapy.
Zhou, Y, Fan, S, Feng, L, Huang, X, Chen, X
Advanced materials (Deerfield Beach, Fla.). 2021;(48):e2104223
Abstract
Chemodynamic therapy (CDT) uses the tumor microenvironment-assisted intratumoral Fenton reaction for generating highly toxic hydroxyl free radicals (•OH) to achieve selective tumor treatment. However, the limited intratumoral Fenton reaction efficiency restricts the therapeutic efficacy of CDT. Recent years have witnessed the impressive development of various strategies to increase the efficiency of intratumoral Fenton reaction. The introduction of these reinforcement strategies can dramatically improve the treatment efficiency of CDT and further promote the development of enhanced CDT (ECDT)-based multimodal anticancer treatments. In this review, the authors systematically introduce these reinforcement strategies, from their basic working principles, reinforcement mechanisms to their representative clinical applications. Then, ECDT-based multimodal anticancer therapy is discussed, including how to integrate these emerging Fenton reinforcement strategies for accelerating the development of multimodal anticancer therapy, as well as the synergistic mechanisms of ECDT and other treatment methods. Eventually, future direction and challenges of ECDT and ECDT-based multimodal synergistic therapies are elaborated, highlighting the key scientific problems and unsolved technical bottlenecks to facilitate clinical translation.
3.
p53 tumor suppressor and iron homeostasis.
Zhang, J, Chen, X
The FEBS journal. 2019;(4):620-629
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Abstract
Iron is an essential nutrient for all living organisms and plays a vital role in many fundamental biochemical processes, such as oxygen transport, energy metabolism, and DNA synthesis. Due to its capability to produce free radicals, iron has deleterious effects and thus, its level needs to be tightly controlled in the body. Deregulation of iron metabolism is known to cause diseases, including anemia by iron deficiency and hereditary hemochromatosis by iron overload. Interestingly, dysregulated iron metabolism occurs frequently in tumor cells and contributes to tumorigenesis. In this review, we will discuss the role of p53 tumor suppressor in iron homeostasis.